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Committee to Evaluate Drugs (CED)
Recommendations and Reasons
May 2008
Sunitinib (for Metastatic Renal Cell Carcinoma)
Product:
SUNITINIB (Sutent®) 12.5mg, 25mg,
50mg capsule
Highlights of Recommendation:
◆
Sunitinib (Sutent) is a new drug
treatment for patients with Metastatic
Renal Cell Carcinoma (MRCC). MRCC is
kidney cancer that has spread to other
parts of the body.
◆
The Committee initially considered
sunitinib (Sutent) in the second-line
treatment of MRCC (i.e., in patients who
have failed or cannot tolerate first-line
therapy). The clinical and economic
evidence for sunitinib (Sutent) for
second-line therapy was not compelling.
Class of drugs:
Multi-kinase inhibitor; anti-cancer agent
Indication:
Treatment of metastatic renal cell
carcinoma (MRCC) or kidney cancer
Manufacturer:
Pfizer Canada Inc.
CED Recommendation
The CED recommended that sunitinib
(Sutent) be funded through the
Exceptional Access Program (EAP) for
the first-line treatment of metastatic
renal cell carcinoma (MRCC) if the
price is reduced. The CED’s
recommendation was made on the
basis that the drug appears to be
more effective and better tolerated
than interferon-alpha for treating
this disease, but is significantly
more expensive.
◆
◆
An interim analysis of a large trial
comparing sunitinib (Sutent) and
interferon-alpha (the current first-line
therapy) supports using sunitinib (Sutent)
as first-line treatment for MRCC. Sunitinib
(Sutent) was shown to improve the
length of time patients were surviving
without disease progression.
◆
Sunitinib (Sutent) was also better
tolerated than interferon-alpha.
◆
However, the high cost of sunitinib
(Sutent) renders the therapy much
less cost-effective when compared
to interferon-alpha for the treatment
of MRCC.
Executive Officer Decision
Taking into consideration the
CED’s review and recommendation
and based on a subsequent
pricing agreement, the Executive
Officer decided to fund sunitinib
(Sutent) as first-line and second-line
treatment for MRCC through the
Exceptional Access Program,
according to specific criteria.
The Committee subsequently considered
the use of sunitinib (Sutent) in first-line
treatment.
◆
Interferon-alpha is currently reimbursed
through the Exceptional Access Program
(EAP) for the treatment of MRCC.
◆
The Committee indicated it is highly likely
that sunitinib (Sutent) would replace
interferon-alpha for treating MRCC if
it is funded.
◆
Overall, the Committee noted that
first-line therapy with sunitinib
(Sutent) appears to be more effective
and better tolerated than interferonalpha. However, sunitinib (Sutent)
therapy is not considered costeffective when compared to
interferon-alpha for the treatment
of MRCC.
◆
Therefore, the Committee recommended
that sunitinib (Sutent) be funded through
the EAP for first-line treatment of MRCC,
if the price is reduced.
Background:
Metastatic renal cell carcinoma is a form
of kidney cancer that has spread beyond
the kidney.
Renal cell cancer can spread to the lungs,
lymph nodes, brain and liver. In about
30 percent of patients, the cancer has
spread or metastasized by the time of
diagnosis. After aggressive surgery, the
first-line, or standard treatment for MRCC
has been with drugs that stimulate the
immune system, such as interferon-alpha
or interleukin-2. However, these drugs are
not suitable for all patients; and interferonalpha appears to be of less benefit than
some newer anti-cancer drugs.
Sunitinib (Sutent) is a new alternative for
patients with MRCC. The drug works by
targeting specific enzymes involved in the
growth and survival or cancer cells. By
disrupting this signalling, sunitinib (Sutent)
prevents renal carcinoma cells from forming
new blood vessels that sustain the growth
of a cancerous tumour.
Status
Funding available through the
Ontario Public Drug Programs via
the Exceptional Access Program.
Ministry of
Health and Long-Term Care
continued…
Detailed Discussion:
◆
In March 2007, the Committee considered
sunitinib (Sutent) for second-line therapy
of MRCC. At that time, the Committee
felt there were no compelling data from
published randomized phase III trials to
support this indication. The Committee
was also concerned about the lack of
pharmacoeconomic data to support
the drug’s cost-effectiveness for secondline treatment.
◆
In June 2007, the Committee considered
the funding of sunitinib (Sutent) for the
first-line treatment of MRCC.
◆
The Committee reviewed studies
evaluating sunitinib (Sutent) for first-line
treatment of MRCC, including the
associated practice guidelines developed
by Cancer Care Ontario’s (CCO’s)
Genitourinary Disease Site Group.
◆
The associated practice guidelines state
that although immunotherapy has been
the standard of care for patients with
inoperable locally advanced or metastatic
renal cell carcinoma, there is now
evidence of important clinical benefit
for agents that inhibit angiogenesis in
this patient population.
◆
The CCO guidelines supporting first-line
treatment include a large randomized
clinical trial (Motzer et al, N Engl J Med
2007 January 11: 356(2):115-124), which
reported significantly longer progressionfree survival with sunitinib (Sutent)
compared with interferon-alpha. At
the time of analysis, the duration of
progression-free survival was a median
of 11 months for patients treated with
sunitinib (Sutent), compared with median
of five months for patients treated with
interferon-alpha; hazard ratio=0.42,
[95% confidence interval (CI), 0.32-0.54];
p-value<0.000001.
◆
The available data on quality of life from
the Motzer et al trial were limited but
suggested patient-reported quality of life,
as assessed by the Functional Assessment
of Cancer Therapy-General (FACT-G), was
better with sunitinib (Sutent). Mean total
FACT-G scores were higher with sunitinib
(Sutent) than interferon-alpha at every
assessment time point.
◆
◆
The most common side effects associated
with sunitinib (Sutent) are fatigue,
diarrhea, nausea, hypertension, and
suppression of blood counts.
The Committee noted that the results
of the pharmacoeconomic analysis
provided by the manufacturer comparing
sunitinib (Sutent) to interferon-alpha for
the treatment of MRCC are above the
threshold where a therapy is typically
considered cost-effective. This is mainly
due to the significantly higher price of
sunitinib (Sutent) in comparison to
interferon alpha ($6,950 per 6-week
cycle versus $4,500 per 12-week cycle).
◆
Overall, the Committee noted that results
from a large phase III randomized clinical
trial show that sunitinib (Sutent) is more
effective and better tolerated when
compared to interferon-alpha in the
first-line treatment for MRCC. However,
using sunitinib (Sutent) for the treatment
of MRCC is not considered cost-effective
when compared to interferon-alpha
therapy. Therefore, the Committee
recommended that sunitinib (Sutent)
be funded through the EAP (Exceptional
Access Program) if the price is reduced.
◆
The CED worked jointly with a
subcommittee involving cancer experts
to review this cancer drug, as is done
for all other cancer drug treatments.
Cancer Care Ontario (CCO) Information:
Information on CCO chemotherapy
regimens for MRCC is available at:
http://www.cancercare.on.ca/
index_chemoRegimensbyDisease.htm
CEDAC Recommendation:
(http://www.cadth.ca/index.php/
en/cdr/recommendations)
The Canadian Expert Drug Advisory
Committee (CEDAC) reviewed sunitinib
(Sutent) for second-line treatment of MRCC
and recommended that it not be listed.
CEDAC did not review sunitinib (Sutent)
for first-line treatment of MRCC.
Sunitinib (Sutent) is funded through the
EAP according to the following criteria:
◆
First-line therapy for patients with
Memorial Sloan Kettering Prognostic
Score of Favourable Risk or an
Intermediate Risk; or
◆
Second-line therapy for patients where
(a) the disease is of clear cell histology;
AND
(b) they have failed first-line cytokinebased therapy.
◆
◆
The prescribed dosage should be 50mg
daily for four (4) weeks, followed by two
(2) weeks off the Drug Product, in
repeated six (6) week cycles.
Renewal criteria: Written confirmation
from the clinician that the patient
has benefited from therapy and is
expected to continue to do so.
Ministry of
Health and Long-Term Care
Ontario Public Drug Programs
For more information, please contact:
Ministry of Health and Long-Term Care
Ontario Public Drug Programs
Hepburn Block, 9th Floor
80 Grosvenor Street, Queen’s Park
Toronto, Ontario M7A 1R3
or click: http://www.health.gov.on.ca/english/
providers/program/drugs/ced_rec_table.html